Abstract

Non-small-cell lung cancer (NSCLC) is one of the most frequent solid tumors and regarded as a significant threat to individual health around the world. MicroRNAs (miRs) are recognized as critical governors of gene expression during carcinogenesis, while their clinical significance and mechanism in NSCLC occurrence and development are required for further investigation. In this report, we characterized the functional role of miR-598 and its regulation mechanism in NSCLC. The expression level of miR-598 in NSCLC tissues and cell lines was detected by qRT-PCR. A549 cells were transiently transfected with miR-598 mimics or miR-598 inhibitors. Scratch assay and Transwell assay were used to detect cell transfection, migration, and invasion. Possible binding sites of miR-598 in MSI2 mRNA were predicted by bioinformatics and validated by dual-luciferase reporter gene system. The ability of migration and invasion was examined on cells transfected with MSI2 alone or cotransfected A549 cells with miR-598. The expression of miR-598 in NSCLC tissues was significantly lower than that in adjacent tissues, and the expression of miR-598 in NSCLC cell lines (A549, H1650, and H1299) was also significantly lower than that of normal lung epithelial cell line BEAS-2B. A549 cells were significantly inhibited in migration and invasion after transfection with miR-598 mimics, while miR-598 inhibitors were significantly enhanced in migration and invasion. MSI2 was a direct target gene of miR-598. MSI2 can promote the migration and invasion of A549 cells, but the ability to promote cell migration and invasion was reversed when miR-598 was introduced. In conclusion, miR-598 inhibits the migration and invasion of NSCLC by downregulating the target gene MSI2.

Highlights

  • Lung cancer is a common malignant tumor of the respiratory system, and the incidence and mortality rates of lung cancer have significantly increased in recent years in China [1]

  • Current research suggested that miRNAs were closely related to the occurrence and development of diseases such as differentiation, proliferation, invasion, and apoptosis of lung cancer cells [19]. miRNAs can downregulate the activity of oncogenes to inhibit tumorigenesis and cancer development [20]

  • Another study claimed that miR-598 functioned as an oncomiR that its overexpression promoted colorectal cancer cell proliferation and cell cycle progression [21]

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Summary

Introduction

Lung cancer is a common malignant tumor of the respiratory system, and the incidence and mortality rates of lung cancer have significantly increased in recent years in China [1]. Widely studied in inhibiting tumor cell growth, migration, and invasion, but its role in the occurrence and development of NSCLC is unclear. MSI2 is highly expressed in the context of pancreatic cancer [16], liver cancer [17], and glioma [18], and its expression level is closely related to the invasion and metastasis of tumor cells. This study investigated the expression of miR-598 in non-small-cell lung cancer tissues and the effect of miRNA598 targeting MSI2 NSCLC cell migration and invasion in order to provide new theoretical basis for the diagnosis and treatment of NSCLC. 500 μL of RPMI-1640 culture medium containing 10% fetal bovine serum (Gibco, Grand Island, NY, USA) was added to the lower chamber, and three replicates were set in each group.

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